title: Tumor- and organ-dependent infiltration by myeloid-derived suppressor cells.
abstract: Myeloid-derived suppressor cells (MDSCs) increase during tumor growth and following cytoreductive therapy resulting in immune dysfunction and tumor escape from host control. We report organ- and tumor-specific expansion of MDSCs, differences in their molecular and membrane phenotypes and T-cell suppressive activity. A significant increase in MDSCs was observed within the spleen, peripheral blood (PB), bone marrow (BM), lungs, and livers of mice bearing orthotopic 4T1, but not CI66 mammary tumors. The PB of 4T1 TB mice had the highest frequency of MDSCs (78.6±2.1%). Similarly, the non-parenchymal cells (NPCs) in the tumor tissue, livers and lungs of 4T1 tumor-bearing (TB) mice had an increased MDSCs frequency. Studies into Gr-1 and Ly-6C staining of MDSCs revealed significant increases in CD11b+Gr-1(dull)Ly-6C(high) and CD11b+Gr-1(bright)Ly-6C(low) subsets. The frequency of MDSCs inversely correlated with the CD3+ T-cell frequency in the spleen, and blood of 4T1 TB mice and was associated with a significant decrease in splenic and NPCs IFN-γ and IL-12 transcript levels, as well as significantly increased levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), granulocyte colony-stimulating factor (G-CSF), interleukin-10 (IL-10), interleukin-13 (IL-13), arginase-1 (ARG-1), nitric oxide synthase (NOS-2), vascular endothelial growth factor-A (VEGF-A) transcripts. In summary, MDSCs are significantly increased not only in lymphoid organs, but also in parenchymal organs including lungs and livers of TB mice, where they may facilitate metastasis to these organ sites.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Younos
authors.forename: Moses
authors.initials: M
authors.lastname: Donkor
authors.forename: Traci
authors.initials: T
authors.lastname: Hoke
authors.forename: Alicia
authors.initials: A
authors.lastname: Dafferner
authors.forename: Holly
authors.initials: H
authors.lastname: Samson
authors.forename: Sherry
authors.initials: S
authors.lastname: Westphal
authors.forename: James
authors.initials: J
authors.lastname: Talmadge
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D005260:Female; D006411:Hematopoiesis, Extramedullary; D007165:Immunosuppression Therapy; D007964:Leukocytosis; D008099:Liver / Q000473:pathology*; D008168:Lung / Q000473:pathology*; D015674:Mammary Neoplasms, Animal / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D019899:Paracrine Communication; D059016:Tumor Microenvironment / Q000276:immunology